The ABC-type multidrug resistance transporter LmrCD is responsible for an extrusion-based mechanism of bile acid resistance in Lactococcus lactis.
نویسندگان
چکیده
Upon prolonged exposure to cholate and other toxic compounds, Lactococcus lactis develops a multidrug resistance phenotype that has been attributed to an elevated expression of the heterodimeric ABC-type multidrug transporter LmrCD. To investigate the molecular basis of bile acid resistance in L. lactis and to evaluate the contribution of efflux-based mechanisms in this process, the drug-sensitive L. lactis NZ9000 DeltalmrCD strain was challenged with cholate. A resistant strain was obtained that, compared to the parental strain, showed (i) significantly improved resistance toward several bile acids but not to drugs, (ii) morphological changes, and (iii) an altered susceptibility to antimicrobial peptides. Transcriptome and transport analyses suggest that the acquired resistance is unrelated to elevated transport activity but, instead, results from a multitude of stress responses, changes to the cell envelope, and metabolic changes. In contrast, wild-type cells induce the expression of lmrCD upon exposure to cholate, whereupon the cholate is actively extruded from the cells. Together, these data suggest a central role for an efflux-based mechanism in bile acid resistance and implicate LmrCD as the main system responsible in L. lactis.
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متن کاملExtrusion-Based Mechanism of Bile Acid Transporter LmrCD Is Responsible for an The ABC-Type Multidrug Resistance
متن کامل
LmrCD is a major multidrug resistance transporter in Lactococcus lactis.
When Lactococcus lactis is challenged with drugs it displays a multidrug resistance (MDR) phenotype. In silico analysis of the genome of L. lactis indicates the presence of at least 40 putative MDR transporters, of which only four, i.e. the ABC transporters LmrA, LmrC and LmrD, and the major facilitator LmrP, have been experimentally associated with the MDR. To understand the molecular basis of...
متن کاملLmrR-mediated gene regulation of multidrug resistance in Lactococcus lactis.
Multidrug resistance (MDR) in Lactococcus lactis is due to the expression of the membrane ATP-binding cassette (ABC) transporter LmrCD. In the absence of drugs, the transcriptional regulator LmrR prevents expression of the lmrCD operon by binding to its operator site. Through an autoregulatory mechanism LmrR also suppresses its own expression. Although the lmrR and lmrCD genes have their own pr...
متن کاملLmrR is a transcriptional repressor of expression of the multidrug ABC transporter LmrCD in Lactococcus lactis.
LmrCD is an ABC-type multidrug transporter in Lactococcus lactis. LmrR encodes a putative transcriptional regulator. In a DeltalmrR strain, lmrCD is up-regulated. LmrR binds the promoter region of lmrCD and interacts with drugs that cause lmrCD up-regulation. This suggests that LmrR is a drug-dependent transcriptional regulator of lmrCD expression.
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ورودعنوان ژورنال:
- Journal of bacteriology
دوره 190 22 شماره
صفحات -
تاریخ انتشار 2008